Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis

Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to p...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2022-12, Vol.11
Main Authors: Wang, Zhongxiao, Yemanyi, Felix, Blomfield, Alexandra K, Bora, Kiran, Huang, Shuo, Liu, Chi-Hsiu, Britton, William R, Cho, Steve S, Tomita, Yohei, Fu, Zhongjie, Ma, Jian-Xing, Li, Wen-Hong, Chen, Jing
Format: Article
Language:English
Subjects:
Amino Acid Transport Systems
Amino Acid Transport Systems, Neutral
Amino acids
Analysis
Angiogenesis
Animal models
Animals
Blood vessels
Cell membranes
Developmental Biology
Diabetic retinopathy
Endothelial Cells
Endothelium
Eye diseases
Gene expression
Genetic transcription
Glutamine
Homeostasis
Humans
Ischemia
Localization
LRP5 protein
Metabolism
Mice
Neovascularization
Neovascularization, Pathologic - genetics
Nutrient uptake
Physiological aspects
Proteins
Retina
Retinopathy
Scientific equipment and supplies industry
SLC38A5
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A
Vascular endothelial growth factor receptor 2
Vascularization
Wnt protein
β-Catenin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. is suppressed in retinal blood vessels from and mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, transcription is regulated by Wnt/β-catenin signaling. Genetic deficiency of in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.
ISSN:2050-084X
2050-084X
DOI:10.7554/ELIFE.73105